TCR-therapy for embryonal cell derived tumors

Embryonal pediatric tumors such as neuroblastoma are notoriously “invisible” to the immune system. Unlike many adult cancers, these tumors arise from cell lineages that do not naturally express key immune-interacting molecules, including MHC-I. Combined with their limited neoantigen pool, neuroblastoma continues to evade detection and persist as an extremely aggressive disease with poor survival rates.

Our research has shown that this “invisibility” can be reversed. We demonstrated that the expression of MHC-I and other immunogenic markers can be induced by using cytokines or histone deacetylase (HDAC) inhibitors. This approach renders neuroblastoma susceptible to immune recognition, creating a vital opportunity for T-cell-based immunotherapy.

In this project, we aim to develop T-cell receptor (TCR) engineered T-cells designed specifically against embryonal tumors. Our approach involves screening of the MHC-I immunopeptidome to identify aberrantly spliced intracellular proteins which may even be shared across various pediatric malignancies. By isolating reactive antigen-specific TCRs, we will then engineer potent new TCR-T cell therapies. Ultimately, our goal is to translate these findings into effective treatments and improve outcomes for children with embryonal tumors.

Contact 
Felicia Amelie